Project Summary There is no dedicated sensory organ for time, and yet our brains are able to use time to anticipate the environment and adapt. The process of interval timing on a seconds to minutes scale is evolutionarily widespread and is central to critical cognitive tasks and behaviors, including how to optimally find food. Despite the importance of this ability, there is no known neural mechanism for interval timing on this scale in any organism. Questions about the neural mechanism of interval timing remain, in part, because a majority of studies record neural activity from only one or a small subset of brain regions. Therefore, to determine the neural mechanism of interval timing requires whole brain imaging and neuronal activity manipulations to identify each neuron in the circuit and their roles. These techniques are extremely difficult in the large vertebrate brain. In contrast, Drosophila are the ideal organism to advance the interval timing field as their compact brains and easy genetic manipulability allow whole brain imaging and precise neuronal perturbations as well as behavioral analysis. This proposal aims to use Drosophila and cutting-edge technologies to achieve the goal of determining the neural mechanism of interval timing from the estimation of time to behavioral output. The central hypothesis for this project is that a coordinated network distributed throughout the brain estimates time and that estimate can be used to guide behavior. The first aim tests the hypothesis that interval timing in Drosophila is encoded using dynamic firing rate changes of a network of neurons throughout the brain. The second aim tests the hypothesis that Drosophila use interval timing to estimate food density and this information is integrated with other cues to alter behavior. These aims will be completed using behavioral assays, whole-brain neuronal activity imaging, and genetic techniques. The information obtained in this project will provide the first demonstration and mechanistic understanding of a distributed timing circuit in any animal.